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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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VII. Pedia Sapiens: A Genesis Future on Earth and in the Heavens

2. A Second Genesis: Life Begins Anew via an EarthWise Respectful Creativity

Renata, Hans, et al. Expanding the Enzyme Universe: Accessing Non-Natural Reactions by Mechanism-Guided Directed Evolution. Angewandte Chemie International Edition. 54/3351, 2015. California Institute of Technology chemical engineers Renate, Jane Wang, and Frances Arnold continue their project (see Arnold Lab publications) to learn how living systems became vitally complex so as to initiate a biomimetic palliative and sustainable phase. See also, for example, The Nature of Chemical Innovation: New Enzymes by Evolution by Frances Arnold in Quarterly Reviews of Biophysics (48/404, 2015).

High selectivity and exquisite control over the outcome of reactions entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature’s known repertoire. In this Review, we outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progression has been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been exploited for chemical synthesis, with an emphasis on reactions that do not have natural counterparts. Non-natural activities can be improved by directed evolution, thus mimicking the process used by nature to create new catalysts. Finally, we describe the discovery of non-native catalytic functions that may provide future opportunities for the expansion of the enzyme universe. (Abstract)

Enzyme: Any of numerous proteins produced in living cells that accelerate or catalyze the metabolic processes of an organism. a substance produced by a living organism that acts as a catalyst to bring about a specific biochemical reaction.

Ronquist, Scott, et al. Algorithm for Cellular Reprogramming. Proceedings of the National Academy of Sciences. 114/11832, 2017. A ten person interdisciplinary team from the University of Michigan, University of Maryland, Harvard University and IXL Learning, Raleigh, NC provide a microcosm of the frontier abilities of genomic and biological research. As the quote cites, a radical new phase is respectfully beginning to take over living systems for all manner of curative benefits and enhancements. This capacity involves “a dynamic systems view of the genome” so as to achieve an intentional employ of nature’s independent, universal source code.

Reprogramming the human genome toward any desirable state is within reach; application of select transcription factors drives cell types toward different lineages in many settings. We introduce the concept of data-guided control in building a universal algorithm for directly reprogramming any human cell type into any other type. Our algorithm is based on time series genome transcription and architecture data and known regulatory activities of transcription factors, with natural dimension reduction using genome architectural features. Our algorithm predicts known reprogramming factors, top candidates for new settings, and ideal timing for application of transcription factors. This framework can be used to develop strategies for tissue regeneration, cancer cell reprogramming, and control of dynamical systems beyond cell biology. (Significance)

Rozhkova, Elena and Katsuhiko Ariga, eds. From Molecules to Materials: Pathways to Artificial Photosynthesis. Heidelberg: Springer, 2016. Elena Rozhkova is a Principal Investigator at the Center for Nanoscale Materials, Argonne National Laboratory, USA, and Katsuhike Ariga is the Director of the Supermolecules Unit, Research Center for Materials Nanoarchitectonics, National Institute for Materials Science, Japan. Typical chapters are Enzymes as Exploratory Catalysts in Artificial Photosynthesis, and From Molecular to Hybrid Nanoconstructs. Our interest is the phenomenal passage of life’s basic usage of solar light energy onto intentional, worldwide human avail and continuance.

This interdisciplinary book focuses on the various aspects transformation of the energy from sunlight into the chemical bonds of a fuel, known as the artificial photosynthesis, and addresses the emergent challenges connected with growing societal demands for clean and sustainable energy technologies. The editors assemble the research of world-recognized experts in the field of both molecular and materials artificial systems for energy production. Contributors cover the full scope of research on photosynthesis and related energy processes.

Schindler, Daniel, et al. Synthetic Genomics: A New Venture to Dissect Genome Fundamentals and Engineer New Function. Current Opinion in Chemical Biology. 46/56, 2018. University of Manchester, Manchester Institute of Biotechnology, UK, and Chinese Academy of Sciences, Institute of Synthetic Biology researchers contribute to this open frontier going forward, as if a second, intentional genesis, to take up and continue life’s evolutionary genetic endowment by learning to (re)write palliative and beneficent editions. See also Recent Advances in DNA Nanotechnology in this journal (46/63). But as I long had a day job as an engineer, this word should rightly be replaced for it is inappropriate as often used. Might one suggest something like “engender” for this quite organic creativity?

Since the first synthetic gene was synthesized in 1970s, the efficiency and the capacity of made-to-order DNA sequence synthesis has increased by several orders of magnitude. Advances in DNA synthesis and assembly over the past years has resulted in a steep drop in price for custom made DNA. Similar effects were observed in DNA sequencing technologies which underpin DNA-reading projects. Today, synthetic DNA sequences with more than 10 000 bps and turn-around times of a few weeks are commercially available. This enables researchers to perform large-scale projects to write synthetic chromosomes and characterize their functionalities in vivo. Synthetic genomics opens up new paradigms to study the genome fundamentals and engineer novel biological functions. (Abstract)

Schmidt, Gregory. The Best Toys That Teach Kids How to Code. New York Times. December 19, 2017. In the week before Christmas, a delightful, illustrated feature about how companies are coming up with encoded building kits such as Think & Learn Code-a-Pillar (Fisher Price), LEGO Boost and FurReal Proto Max (Hasbro). Another source is Kodable who crafts programming experiences for elementary schools. A toy tester site named Wirecutter can be accessed which notes a learning center in San Francisco named the Makery. To scale up many levels, might we adults be able to learn and imagine a “Kodable Kosmos” by way of our human universe genome HUG project?

Schmidt, Markus, et al, eds. Synthetic Biology: The Technoscience and its Societal Consequences. Dordrecht: Springer, 2009. A report on a European project to provide considerate guidance for an increasing human ability to “reengineer” the very molecular, genetic, and cellular basis of life. A companion 2010 volume might be Synthetic Biology: Building on Nature’s Inspiration from the National Academy of Sciences. From any historic, philosophical, or religious perspective this is a fantastic prospect in our midst, no less than the advent of a “new creation” as composite human inquiry and knowledge might take over, as seemingly intended, the cosmic evolutionary genesis.

Shang, Yorke, et al. A Semi-Synthetic Organism that Stores and Retrieves Increased Genetic Information. Nature. 551/644, 2017. This entry by nine Scripps Research Institute biochemists led by Floyd Romesberg (herein) has been cited as the forefront of advances into this sudden new phase of intentionally while ethically rescripting and recrafting life’s prior evolutionary biochemical, genomic, anatomic and physiological nature.

Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is the creation of semi-synthetic organisms whose DNA harbours two additional letters that form a third, unnatural base pair. Here we report the in vivo transcription of DNA containing dNaM and dTPT3 into mRNAs with two different unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient decoding at the ribosome to direct the site-specific incorporation of natural or non-canonical amino acids into superfolder green fluorescent protein. The results demonstrate that interactions other than hydrogen bonding can contribute to every step of information storage and retrieval. The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions. (Abstract excerpt)

Singer, Emily. New Letters Added to the Genetic Alphabet. Quanta Magazine. July, 2015. Yes, another report about novel abilities to modify life’s genome endowment, in this case by biochemist Steven Benner’s Foundation for Applied Molecular Laboratory in Florida. But an auspicious difference, the advance involves “better blueprints for life” via additions of two synthetic nucleotides to evolution’s ATCG version. The technical reference is Structural Basis for a Six Nucleotide Genetic Alphabet by Millie Georgiadis, et al in the Journal of the American Chemical Society 137/6947, 2015. And the natural philosophy import is awesome. Collaborative human beings just now appear over a planetary surface whom are able to discern nature’s generative program. As a result, it can pass to their intentional rewrite, so as to take over and greatly enhance the organic material procreation of a genesis cosmos.

Sole, Ricard. Synthetic Transitions: Towards a New Synthesis. Sante Fe Institute Working Papers. 16-06-009, 2016. The Barcelona systems scientist avails the popular major evolutionary transitions scale to broach paths toward its intentional procreative continuance. The entry also appears as the lead article in a special Major Synthetic Evolutionary Transitions issue in the Philosophical Transactions of the Royal Society (371/20160175, 2016). A conceptual basis would then be a carry forth of intrinsic design principles which are being found to recur in kind at each prior stage. A modicum of “universal laws and traits,” along with an “algorithmic logic” is employed in its service. Various sections consider synthetic phases of prebiotic chemistry, replicators, genetics, cells, multicellularity, symbiosis, cognitive agents, languages, minds, and ecosystems, which are seen to readily iterate and emerge. Akin to Eric Smith and Harold Morowitz’s 2016 The Origin and Nature of Life on Earth (noted in reference 301) life’s natural development is best seen to proceed from physical realms by way of nested phase transitions. See also Synthetic Collective Intelligence by RS, et al in BioSystems (2016, search).

The evolution of life in our biosphere has been marked by several major innovations. Such major complexity shifts include the origin of cells, genetic codes or multicellularity to the emergence of non-genetic information, language or even consciousness. Understanding the nature and conditions for their rise and success is a major challenge for evolutionary biology. Along with data analysis, phylogenetic studies and dedicated experimental work, theoretical and computational studies are an essential part of this exploration. With the rise of synthetic biology, evolutionary robotics, artificial life and advanced simulations, novel perspectives to these problems have led to a rather interesting scenario, where not only the major transitions can be studied or even reproduced, but even new ones might be potentially identified. In both cases, transitions can be understood in terms of phase transitions, as defined in physics. Such mapping (if correct) would help defining a general framework to establish a theory of major transitions, both natural and artificial. Here we review some advances made at the crossroads between statistical physics, artificial life, synthetic biology and evolutionary robotics. (Abstract)

Sole, Ricard. The Major Synthetic Evolutionary Transitions. Philosophical Transactions of the Royal Society B. 371/20160175, 2016. An introduction to an issue about this title subject which attests how much this view of life’s emergent, recurrent scale from replicative biochemicals to cells, organisms, brains, primates and onto linguistic cultures is an established paradigm. Ricard, an ICREA Complex Systems group leader at the Universitat Pompeu Fabra, Barcelona, is in pursuit of, with many colleagues (search RS), its salutary extension by way of natural biomimetic principles. His lead paper, Synthetic Transitions, is reviewed at length herein. A dozen authoritative entries follow such as Some Mechanistic Requirements for Major Transitions by Peter Schuster, Generating Minimal Living Systems from Non-Living Materials by Steen Rasmussen, et al, Biogeneric Developmental Processes: Drivers of Major Transitions in Animal Evolution by Stuart Newman, Agent-Based Models for the Emergence and Evolution of Grammar by Luc Steels (search), Energy and Time Determine Scaling in Biological and Computer Designs by Melanie Moses, et al, and Synthetic Consciousness by Paul Verschure. OK

Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined. (Abstract)

Srinivas, Niranjan, et al. Enzyme-free Nucleic Acid Dynamical Systems. Science. 358/1401, 2018. We cite because CalTech, University of Washington, and UT Austin researchers including Erik Winfree advance understandings of the broad range of functional qualities that DNA nucleotide biomolecules innately seem to possess. These natural biochemicals are being found to have uniquely adaptable properties for all manner of structural formations, which our nascent human ingenuity can continue forth into a new biogenetic procreation.

Chemistries exhibiting complex dynamics—from inorganic oscillators to gene regulatory networks—have been long known but either cannot be reprogrammed at will or rely on the sophisticated enzyme chemistry underlying the central dogma. Can simpler molecular mechanisms, designed from scratch, exhibit the same range of behaviors? Abstract chemical reaction networks have been proposed as a programming language for complex dynamics, along with their systematic implementation using short synthetic DNA molecules. We developed this technology for dynamical systems by identifying critical design principles and codifying them into a compiler automating the design process. Using this approach, we built an oscillator containing only DNA components, establishing that Watson-Crick base-pairing interactions alone suffice for complex chemical dynamics and that autonomous molecular systems can be designed via molecular programming languages. (Abstract)

The programmable nature of base-pairing interactions and the minimal requirements on the chemical environment make DNA a particularly attractive engineering material. Nucleic acids as chemical controllers naturally integrate with the ever-expanding range of molecular structures, machines, and devices developed in DNA nanotechnology and could eventually be embedded within complex synthetic organelles or artificial cells that sense, compute, and respond to their chemical and molecular environment. Besides addressing a technological challenge, we also answer a fundamental scientific question, showing that Watson-Crick base pairing alone suffices for complex temporal dynamics. (Conclusion)

Srinvasarao, Mohan, et al. Biologically Inspired Far-from-Equilibrium Materials. MRS Bulletin. 44/2, 2019. In this international Materials Research Society main publication, systems chemists MS, Georgia Tech, Germano Iannacchione, Worcester PolyTech, and Atad Parikh, UC Davis introduce a special issue with this title. What is notable today is a fertile integration and avail of these life-like, thermodynamic energies and activities into this older inorganic, metallurgical field. See also herein, Bioinspired Nonequilibrium Search for Novel Materials by Arvind Murugan and Heinrich Jaeger, and Nature’s Functional Nanomaterials by Bodo Wilts, et al.

Traditional approaches to materials synthesis have largely relied on uniform, equilibrated phases leading to static “condensed-matter” structures. Departures from these modes of materials design are pervasive in biology. From the folding of proteins to the reorganization of self-regulating cytoskeletal networks, biological materials reflect a major shift in emphasis from equilibrium thermodynamics to out-of-equilibrium regimes. Here, highly structured dynamical states that are out of equilibrium facilitate the creation of new materials capable of performing life-like functions such as complex and cooperative processes, self-replication, and self-repair, ultimately biological principles of spatiotemporal modes of self-assembly. (Srinvasarao Abstract excerpts)

Searching for materials with improved or novel properties involves an iterative process to successively narrow the gap between some initial starting point and the desired design target. This can be viewed as an optimization problem in a high-dimensional space, often with dozens of material parameters that need to be tuned. To tackle this, the evolutionary process in biology has been a source of inspiration for effective search algorithms. Here, we go beyond black box algorithms and take a broader view of computational evolution strategies. We discuss recent strategies that exploit knowledge about the material configuration statistics and highlight advantages by way of time-varying environments. Throughout, we emphasize that the search strategies themselves can be viewed as a nonequilibrium dynamical process in design space. (Murugan Abstract)

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